Ring-expansion reaction of cyano-substituted singlet phenyl nitrenes: Theoretical predictions and kinetic results from laser flash photolysis and chemical trapping experiments

Article abstract of DOI:10.1021/ja002594b

On the basis of the open-shell electronic structure of the lowest-singlet state of phenylnitrene, it is predicted that substitution of a radical-stabilizing cyano group at an ortho carbon should facilitate cyclization at that carbon, whereas cyano substitution at the para carbon should retard the rate of cyclization. These qualitative predictions have been tested computationally by performing (8/8)CASSCF and CASPT2/6-31G* ab initio calculations and experimentally by carrying out laser flash photolysis and chemical trapping studies. The calculations and experiments both find that, unlike the case with ortho fluoro and ortho methyl substituents, the rate of cyclization at a substituted carbon is not retarded by an ortho cyano group. In contrast, a para cyano group is found, both computationally and experimentally, to raise the barrier to cyclization of singlet phenylnitrene by > 1 kcal/mol.

Full text of DOI:10.1021/ja002594b

J. Am. Chem. Soc. 2001, 123, 1425-1433
1425
Ring-Expansion Reaction of Cyano-Substituted Singlet Phenyl
Nitrenes: Theoretical Predictions and Kinetic Results from Laser
Flash Photolysis and Chemical Trapping Experiments
Nina P. Gritsan,*,| Igor Likhotvorik,† Meng-Lin Tsao,† Nil C¸ elebi,† Matthew S. Platz,*,†
William L. Karney,§ Carl R. Kemnitz,‡ and Weston Thatcher Borden*,‡
Contribution from the Newman and Wolfrom Laboratory of Chemistry, Ohio State UniVersity,
100 West 18th AVenue, Columbus, Ohio 43210, the Department of Chemistry, UniVersity of San Francisco,
2130 Fulton Street, San Francisco, California 94117-1080, the Department of Chemistry, Box 351700,
UniVersity of Washington, Seattle, Washington 98195-1700, and Institute of Chemical Kinetics and
Combustion and NoVosibirsk State UniVersity, 630090 NoVosibirsk, Russia
ReceiVed July 14, 2000. ReVised Manuscript ReceiVed October 31, 2000
Abstract: On the basis of the open-shell electronic structure of the lowest-singlet state of phenylnitrene, it is
predicted that substitution of a radical-stabilizing cyano group at an ortho carbon should facilitate cyclization
at that carbon, whereas cyano substitution at the para carbon should retard the rate of cyclization. These
qualitative predictions have been tested computationally by performing (8/8)CASSCF and CASPT2/6-31G*
ab initio calculations and experimentally by carrying out laser flash photolysis and chemical trapping studies.
The calculations and experiments both find that, unlike the case with ortho fluoro and ortho methyl substituents,
the rate of cyclization at a substituted carbon is not retarded by an ortho cyano group. In contrast, a para
cyano group is found, both computationally and experimentally, to raise the barrier to cyclization of singlet
phenylnitrene by >1 kcal/mol.
Starting with the first reports by Huisgen1a,b and Doering,1c
the chemistry of aryl nitrenes has been the subject of numerous
investigations.2 Singlet phenylnitrene (11) undergoes ring expan-
sion to azacycloheptatetraene (3) via the intermediacy of
azabicyclo[4.1.0]heptatriene (2, Scheme 1).3 With only rare
exceptions,4 the bicyclic intermediates in the ring-expansion
reactions of aryl nitrenes cannot be observed or chemically
trapped, suggesting that the cyclization step in Scheme 1 is rate-
determining (i.e., kC , kE).
This hypothesis is supported by the results of ab initio
calculations.5 In nearly exact agreement with the experimental
1
value for the barrier to the cyclization of 1 to 2 (5.6 ( 0.3
kcal/mol),3i,k the best computational estimate is ∼6 kcal/mol,
and the calculations also find that the barrier to the ring opening
of 2 to 3 is only about half as large.
Substituent effects on the ring-expansion reactions of phe-
nylnitrene have been studied. Banks and co-workers discovered
that bimolecular reactions of singlet pentafluorophenylnitrene
compete successfully with ring expansion.6 Platz and co-workers
have shown that it is the fluorines at the two ortho carbons
which raise the barrier to cyclization of the perfluorinated
nitrene.3e,h,7 Two ortho methyl groups also reduce the rate of
cyclization.8
† Ohio State University.
§ University of San Francisco.
‡University of Washington.
| Institute of Chemical Kinetics and Combustion.
(1) (a) Huisgen, R.; Vossius, D.; Appl, M. Chem. Ber. 1958, 91, 1. (b)
Huisgen, R.; Appl, M. Chem. Ber. 1958, 91, 12. (c) Doering, W. v. E.;
Odum, R. A. Tetrahedron 1966, 22, 81.
(2) Reviews: (a) Smith, P. A. S. In Nitrenes; Lwowski, W., Ed.; Wiley-
Interscience: New York, 1970; Chapter 4. (b) Scriven, E. F. V. In ReactiVe
Intermediates; Abramovitch, R. A., Ed.; Plenum: New York, 1982; Vol.
2, Chapter 1. (c) Wentrup, C. ReactiVe Molecules; Wiley-Interscience: New
York, 1984; Chapter 4. (d) Platz, M. S. In Azides and Nitrenes: ReactiVity
and Utility; Scriven, E. F. V., Ed.; Academic: New York, 1984; Chapter
7. (e) Platz, M. S.; Maloney, V. M. In Kinetics and Spectroscopy of
Carbenes and Biradicals; Platz, M. S., Ed.; Plenum: New York, 1990; pp
303-320. (f) Platz, M. S.; Leyva, E.; Haider, K. Org. Photochem. 1991,
11, 367. (g) Schuster, G. B.; Platz, M. S. AdV. Photochem. 1992, 17, 69.
(h) Platz, M. S. Acc. Chem. Res. 1995, 28, 487. (i) Borden, W. T.; Gritsan,
N. P.; Hadad, C. M.; Karney, W. L.; Kemnitz, C. R.; Platz, M. S. Acc.
Chem. Res. 2000, 33, 765.
(3) (a) Chapman, O. L.; LeRoux, J.-P. J. Am. Chem. Soc. 1978, 100,
282. (b) Schrock, A. K.; Schuster, G. B. J. Am. Chem. Soc. 1984, 106,
5228. (c) Donnelly, T.; Dunkin, I. R.; Norwood, D. S. D.; Prentice, A.;
Shields, C. J.; Thomson, P. C. P. J. Chem. Soc., Perkin Trans. 2 1985,
307. (d) Leyva, E.; Platz, M. S. Tetrahedron Lett. 1985, 26, 2147. (e) Leyva,
E.; Platz, M. S.; Persy, G.; Wirz, J. J. Am. Chem. Soc. 1986, 108, 3783. (f)
Shields, C. J.; Chrisope, D. R.; Schuster, G. B.; Dixon, A. J.; Poliakoff,
M.; Turner, J. J. J. Am. Chem. Soc. 1987, 109, 4723. (g) Li, Y.-Z.; Kirby,
J. P.; George, M. W.; Poliakoff, M.; Schuster, G. B. J. Am. Chem. Soc.
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Am. Chem. Soc. 1993, 115, 8609. (i) Gritsan, N. P.; Yuzawa, T.; Platz, M.
S. J. Am. Chem. Soc. 1997, 119, 5059. (j) Born, R.; Burda, C.; Senn, P.;
Wirz, J. J. Am. Chem. Soc. 1997, 119, 5061. (k) Gritsan, N. P.; Zhu, Z.;
Hadad, C. M.; Platz, M. S. J. Am. Chem. Soc. 1999, 121, 1202.
When, as in 14a,8b only one ortho methyl substituent is
present, cyclization is almost as fast as in unsubstituted
phenylnitrene, because attack occurs preferentially at the un-
substituted ortho carbon to form 5a, rather than 6a.9a When, as
in 14b,10 only one ortho fluoro substituent is present, cyclization
also occurs preferentially at the unsubstituted ortho carbon to
1
form 5b.9b Although, at 298 K cyclization of 4b is 8 times
1
slower than in unsubstituted phenylnitrene, cyclization of 4b
is still 30 times faster than in 2,6-difluorophenylnitrene.
CASSCF and CASPT2/6-31G* calculations have reproduced
these experimental findings and, in fact, predicted some of them
10.1021/ja002594b CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/24/2001

1426 J. Am. Chem. Soc., Vol. 123, No. 7, 2001
Gritsan et al.
Scheme 1
before the experiments were performed.11 For example, the
calculations correctly predicted not only that cyclization of
singlet o-fluorophenylnitrene (14b) would occur at the unsub-
stituted ortho carbon, forming 5b,9b but also that cyclization at
this carbon would encounter a barrier 0.9 kcal/mol higher than
that for cyclization of unsubstituted phenylnitrene.10b Although
the existence of small electronic effects on the barriers to
cyclization was acknowledged, the computational results were
interpreted as indicating that steric effects play the major role
in raising the barriers to cyclization at substituted ortho carbons.
The apparent absence of large electronic effects on the
cyclization reactions of derivatives of phenylnitrene12 was
attributed to the electronic structure of the lowest-singlet state.11
Minimization of the Coulombic repulsion between the two
electrons of opposite-spin in the nonbonding molecular orbitals
(NBMOs) results in this state of phenylnitrene resembling a
cyclohexadienyl radical, with an iminyl radical center doubly
bonded to the remaining ring carbon.13 Therefore, cyclization
of 11 and 14 only requires movement of the imino nitrogen out
of the molecular plane, allowing it to form a bond to the 2p-π
orbital on one of the two ortho carbons, where an electron of
opposite spin appears.
the larger size of cyano relative to hydrogen. Therefore, attack
at a substituted ortho carbon is more likely to occur when the
substituent is cyano, rather than a less radical-stabilizing
substituent, such as fluoro or methyl.
Consistent with this hypothesis, Smalley and co-workers have
found that singlet o-cyanophenylnitrene (14c) undergoes ring
expansion to afford not only 5c, the product formed by
cyclization away from the cyano substituent, but also 6c, the
product formed by cyclization toward the cyano group.14a
Similar results have been found in the ring expansion of singlet
o-acetylphenylnitrene.14b
Because no unpaired spin appears at the meta carbons of 11,
a cyano substituent at one of these carbons would be anticipated
to have only a small effect on the barrier to cyclization at either
of the two, nonequivalent ortho carbons, especially since meta
fluoro10b substitution does not influence the rate constant for
cyclization of phenylnitrene. However, if a para cyano sub-
stituent tends to localize spin at the carbon to which it is
attached, the concomitant decrease in unpaired spin density at
the ortho carbons would be expected to raise the barrier to
cyclization.
To test these qualitative predictions, we have performed ab
initio calculations, laser flash photolysis experiments, and
chemical trapping studies. In this paper we report the results of
these combined theoretical and experimental investigations.
One might expect that a radical-stabilizing, ortho or para
substituent, such as a cyano group, would tend to localize the
unpaired π electron in the six-membered ring at the carbon to
which the substituent is attached. This localization should make
attack by the nitrogen at the cyano-substituted ortho carbon in
14c electronically more favorable than attack at the unsubstituted
ortho carbon, thus tending to counteract the steric effect due to
Computational Methodology
Geometry optimizations were performed with the 6-31G*
basis set,15 using complete active space (CAS)SCF calcula-
tions.16 An eight-electron, eight-orbital active space, hereafter
designated (8/8), was used for all species. The (8/8) active space
for the reactants consisted of seven π MOs, plus the in plane
2p AO on nitrogen. The active space for the transition states
and products consisted of six orbitals that were mainly π in
character plus a σ /σ* pair for the incipient azirine C-N bond.
(8/8)CASSCF/6-31G* vibrational frequencies were calculated
for all stationary points to verify whether each was an
intermediate or a transition state. The unscaled (8/8)CASSCF
frequencies were also used to compute the zero-point vibrational
corrections to the energies. The CASSCF calculations were
performed using the Gaussian 94 suite of programs.17 The
geometries, absolute energies, and vibrational corrections for
all of the stationary points are available as Supporting Informa-
tion.
(4) (a) Carroll, S. E.; Nay, B.; Scriven, E. F. V.; Suschitzky, H.; Thomas,
D. R. Tetrahedron Lett. 1977, 3175. (b) Dunkin, I. R.; Thomson, P. C. P.
J. Chem. Soc., Chem. Commun. 1980, 499. (c) Nielson, P. E.; Buchardt, O.
Photochem. Photobiol. 1982, 35, 317. (d) Younger, C. G.; Bell, R. A. J.
Chem. Soc., Chem. Commun. 1992, 359. (e) Morawietz, J.; Sander, W. J.
Org. Chem. 1996, 61, 4351.
(5) Karney, W. L.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 1378.
(6) (a) Banks, R. E.; Sparkes, G. R. J. Chem. Soc., Perkin Trans. 1 1972,
2964. (b) Banks, R. E.; Prakash, A. Tetrahedron Lett. 1973, 99. (c) Banks,
R. E.; Prakash, A. J. Chem. Soc., Perkin Trans. 1 1974, 1365.
(7) (a) Poe, R.; Grayzar, J.; Young, M. J. T.; Leyva, E.; Schnapp, K.;
Platz, M. S. J. Am. Chem. Soc. 1991, 113, 3209. (b) Poe, R.; Schnapp, K.;
Young, M. J. T.; Grayzar, J.; Platz, M. S. J. Am. Chem. Soc. 1992, 114,
5054. (c) Marcinek, A.; Platz, M. S. J. Phys. Chem. 1993, 97, 12674. (d)
Marcinek, A.; Platz, M. S.; Chan, S. Y.; Floresca, R.; Rajagopalan, K.;
Golinski, M.; Watt, D. J. Phys. Chem. 1994, 98, 412. (e) Gritsan, N. P.;
Zhai, H. B.; Yuzawa, T.; Karweik, D.; Brooke, J.; Platz, M. S., J. Phys.
Chem. A 1997, 101, 2833.
(8) (a) Dunkin, I. R.; Donnelly, T.; Lockhart, T. S. Tetrahedron Lett.
1985, 26, 359. (b) Gritsan, N. P.; Gudmundsdo´ttir, A. D.; Tigelaar, D.;
Platz, M. S. J. Phys. Chem. A 1999, 103, 3458.
(9) (a) Sundberg, R. J.; Suter, S. R.; Brenner, M. J. Am. Chem. Soc.
1972, 94, 513. (b) Leyva, E.; Sagredo, R. Tetrahedron 1998, 54, 7367.
(10) (a) Schnapp, K. A.; Poe, R.; Leyva, E.; Soundararajan, N.; Platz,
M. S. Bioconjugate Chem. 1993, 4, 172. (b) Gritsan, N. P.; Gudmundsdo´ttir,
A. D.; Tigelaar, D.; Zhu, Z.; Karney, W. L.; Hadad, C. M.; Platz, M. S. J.
Am. Chem. Soc. Manuscript submitted.
CASPT2/6-31G* calculations18 were performed at the (8,8)-
CASSCF/6-31G* stationary point geometries. The CASPT2
calculations were carried out with MOLCAS.19 Because the
CASPT2 calculations include dynamic electron correlation,20
but the CASSCF calculations do not, we deem the CASPT2
results to be the more accurate.
(11) Karney, W. L.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 3347.
(12) Gritsan, N. P.; Tigelaar, D.; Platz, M. S. J. Phys. Chem. A 1999,
103, 4465.
(13) (a) Kim, S.-J.; Hamilton, T. P.; Schaefer, H. F. J. Am. Chem. Soc.
1992, 114, 5349. (b) Hrovat, D. A.; Waali, E. E.; Borden, W. T. J. Am.
Chem. Soc. 1992, 114, 8698. (c) Castell, O.; Garc´ıa, V. M.; Bo, C.; Caballol,
R. J. Comput. Chem. 1996, 17, 42.
(14) (a) Lamara, K.; Redhouse, A. D.; Smalley, R. K.; Thompson, J. R.
Tetrahedron 1994, 50, 5515. (b) Berwick, M. A. J. Am. Chem. Soc. 1971,
93, 5780.
(15) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213.
(16) (a) Roos, B. O. AdV. Chem. Phys. 1987, 69, 339. (b) Roos, B. O.
Int. J. Quantum Chem. Symp. 1980, 14, 175.

Cyano-Substituted Singlet Phenyl Nitrenes
J. Am. Chem. Soc., Vol. 123, No. 7, 2001 1427
Table 1. (8/8)CASSCF and CASPT2/6-31G* Energies (kcal/mol),a
Relative to the Reactants, for the Transition Structures and Products
in the Cyclization Reactions of Singlet Phenylnitrene (11) and of the
o- (14c), m- (14d), p- (14e), and 2,6-Dicyano (14f) Derivatives
opening is also computed to require passage over a 2-3 kcal/
mol lower energy barrier than reversion of the intermediates to
the reactants. Therefore, cyclization is the rate determining step
in the ring expansion reactions of 11 to 3 and of 14 to derivatives
of 7 and 8 (Scheme 2).
cyclization
CASSCF
CASPT2
nitrene
modeb
azirine TS product TS product
Of particular interest are the results in Table 1 for cyclization
of singlet o-cyanophenylnitrene (14c). The barrier to cyclization
of 14c away from the cyano substituent to give 5c is calculated
to be about the same as that for cyclization of 11, and the barrier
to cyclization of 14c toward the cyano substituent to give 6c is
predicted to be either about the same as (CASSCF) or slightly
11
-
2
8.9
8.3
8.4
8.6
8.1
4.7
4.5
2.6
4.4
2.9
5.0
3.1
8.6
8.6
7.5
8.2
7.6 -0.7
9.8
8.0
1.6
2.2
0.3
1.2
o-cyano (14c)
away from 5c
toward 6c
away from 5d
m-cyano (14d)
toward
-
-
6d
para-cyano (14e)
2,6-dicyano (14f)
5e ) 6e 9.4
5f ) 6f 8.2
3.3
1.5
1
lower than (CASPT2) the barrier to cyclization of 4c away
from the cyano group. This prediction is very different from
the computational11 and experimental results for cyclization of
o-methylphenylnitrene (14a)8b,9a and o-fluorophenylnitrene
(14b),9b,10b where cyclization away from the ortho substituent
to give 5a or 5b is strongly preferred over cyclization toward
the substituent to give 6a or 6b. However, as noted in the
Introduction, the predicted formation of 6c, as well as that of
5c, in the cyclization of 14c has already been confirmed
experimentally.14a
This difference between 4c and 4a or 4b can reasonably
be attributed to the greater ability of cyano, compared to that
of methyl or fluoro, to localize the electron in the π NBMO at
the ortho carbon to which the substituent is attached. Neverthe-
less, one might wonder to what extent product stability affects
the cyclization barriers. For example, presumably for the same
reason that 6b is computed to be lower in energy than 5b,11
cyclization product 6c is calculated to be 1.9 kcal/mol lower in
energy than cyclization product 5c. This thermodynamic prefer-
ence for forming 6c, rather than 5c, could play a role in the
lower kinetic barrier computed for rearrangement of 4c to 6c
than to 5c.
a Including zero-point energy (ZPE) corrections which range from
-0.3 to 0.1 kcal/mol for transition structures and from 0.9 to 1.4 kcal/
mol for products. b Mode of cyclization, toward or away from the
substituted carbon.
Computational Results
Table 1 summarizes our CASSCF and CASPT2/6-31G*
results for the cyclization reactions of o-, m-, p-, and 2,6-
dicyanophenylnitrene (14c-f). The zero-point corrected energies
of the two possible products, 5 and 6, are given, relative to the
reactants. Also shown are the relative energies of the transition
structures, TS (14f5) and TS (14f6), leading to each of the
products. For comparison, the CASSCF and CASPT2 relative
energies for the cyclization reactions of unsubstituted phenylni-
trene (11)5 are given, too.
As discussed previously,5 CASSCF and CASPT2 calculations
both overestimate the stability of the open-shell electronic
structure of 11 by 2-3 kcal/mol. This is shown by comparison
of the CASSCF and CASPT2 activation energies for cyclization
of 11 to 2 with the results of both multireference CISD
calculations and the experimental value.3i,k However, comparison
of the previously calculated CASSCF and CASPT2 barrier
heights for methyl and fluoro substituents11 with the experi-
mental values measured by Gritsan and Platz and co-workers8b,10b
shows that the calculations do a good job in predicting the
differences between the activation energies for cyclization away
from and toward an ortho substituent.
1
1
1
However, despite the fact that 6b is computed to be lower in
energy than 5b by 6.0 kcal/mol,11the CASPT2 barrier connecting
14b to 6b is 2.8 kcal/mol higher than the barrier connecting
14b to 5b. Therefore, the 1.9 kcal/mol lower energy of 6c,
relative to 5c, is probably not the principal reason the CASPT2
barrier for formation of 6c is computed to be 1.1 kcal/mol lower
than that for formation of 5c.
Inspection of the data in Table 1 reveals that, with one
exception, the cyclization reactions of 11 and 14 are all computed
to be slightly endothermic. At the CASPT2 level the endother-
micity is computed to range from 0.3 to 3.3 kcal/mol. The single
exception is cyclization of 14d to 16d, which is calculated to be
exothermic by -0.7 kcal/mol. Presumably, the extended linear
conjugation in the product is responsible for the CASPT2 finding
that this cyclization reaction is thermodynamically more favor-
able than any of the others.
Since cyclization at the substituted carbon in 14c is predicted
to be slightly faster than cyclization at the unsubstituted carbon,
it seems likely that cyclization of singlet 2,6-dicyanophenylni-
trene (14f) would also be computed to be slightly faster than
that of unsubstituted phenylnitrene (11). However, with cyano
1
groups at both ortho carbons, as in 4f, the unpaired π spin
density at each of these carbons should be smaller than at the
1
single, cyano-substituted, ortho carbon in 4c. Therefore, the
barrier to cyclization might be expected to be somewhat higher
In contrast to the cyclization reactions, electrocyclic ring
opening of the cyclization products (2, 5, and 6) is calculated
to be exothermic by 1-4 kcal/mol at the CASPT2 level.5,21 Ring
1
1
for 4f than for 4c.
Table 1 shows that these two qualitative predictions about
1
the height of the barrier to cyclization of 4f, relative to the
barriers for cyclization of 11 and 14c, are confirmed by the results
ofourcalculations.Incontrast,calculations11 andexperiments3e,i,7,10
both find that 2,6-difluorophenylnitrene cyclizes much more
slowly than 11 and than singlet o-fluorophenylnitrene (14b). As
already noted, unlike the case with a cyano substituent,
cyclization at a fluorinated ortho carbon has a considerably
higher barrier than cyclization at an unfluorinated ortho carbon.
Unlike the case in either 4c or 4f, in the cyclization of
m-cyanophenylnitrene (14d) steric effects are unlikely to play
a significant role in the transition state. In addition, since the
cyano group is on a carbon at which the π NBMO in the reactant
(17) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G.
A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski,
V. G.; Ortiz, J. V.; Foresman, J. B.; Peng, C. Y.; Ayala, P. Y.; Chen, W.;
Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-
Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian 94, Revision B.3; Gaussian,
Inc.: Pittsburgh, PA, 1995.
(18) Andersson, K.; Malmqvist, P.-Å.; Roos, B. O. J. Chem. Phys. 1992,
96, 1218.
1
1
(19) Andersson, K.; Blomberg, M. R. A.; Fu¨lscher, M. P.; Karlstro¨m,
G.; Lindh, R.; Malmqvist, P.-Å.; Neogra´dy, P.; Olsen, J.; Roos, B. O.; Sadlej,
A. J.; Schu¨tz, M.; Seijo, L.; Serrano-Andre´s, L.; Siegbahn, P. E. M.;
Widmark, P.-O. MOLCAS-4; University of Lund: Sweden.
(20) Review: Borden, W. T.; Davidson, E. R. Acc. Chem. Res. 1996,
29, 67.
(21) Karney, W. L.; Kemnitz, C. R.; Borden, W. T. Unpublished results.

1428 J. Am. Chem. Soc., Vol. 123, No. 7, 2001
Gritsan et al.
Scheme 2
has a node, it also seems unlikely that radical stabilization will
influence whether 14d cyclizes to 5d or 6d. In fact, the barrier
heights connecting 14d to 5d and 6d are quite comparable; and
the 0.6 kcal/mol kinetic preference that is predicted for
cyclization of 14d to 6d could be due, at least in part, to the 1.9
kcal/mol lower energy that is computed for the linearly
conjugated product (6d) than for the cross-conjugated product
(5d).
unpaired electron in the π NBMO by the para cyano group in
1
14e than by the meta cyano group in 4d.
In the cyclization products formed from 14c-e, the energetic
advantage of p-cyanophenylnitrene (14e) over both the ortho
(14c) and meta (14d) isomers is lost. Consequently, the energy
of the cyclization product, relative to the nitrene from which it
is formed, is higher for the cyclization product (5e) formed from
14e than for the cyclization products formed from either 14c or
14d. In the transition states for the cyclization of these three
cyanophenylnitrenes, partial loss of the energetic advantage of
14e over both 14c and 14d is the reason the barrier to cyclization
of the para isomer is predicted to be larger than those for either
ortho or meta.
Table 1 shows that the CASPT2 barrier for cyclization of
p-cyanophenylnitrene (14e) is more than 1 kcal/mol higher than
that for cyclization of the ortho (14c) or meta (14d) isomers. In
addition, the energy of the cyclization product, relative to the
1
reactant, is higher for 4e f 5e than for cyclization of either
1
14c or 4d. Both facts are attributable to the lower energy of
1
1
14e compared to that of either 4c or 4d.
Experimental Results
Comparison of the absolute CASPT2 energies of 14c-e
(available in the Supporting Information) reveals that 4e is
1
The computational results in Table 1 predict: (a) a larger
barrier to cyclization for 14e than for 14c, 14d, 14f, or
unsubstituted phenylnitrene (11), (b) a slightly larger barrier to
formation of 5c than 6c in cyclization of 14c, and (c) a slightly
lower barrier to cyclization for both 14c and 14f than for 11. To
test these predictions, we undertook a series of laser flash
photolysis and chemical trapping experiments.
Laser flash photolysis (LFP) of o-cyanophenyl azide in
pentane at 295 K produces a transient spectrum containing a
broad absorption between 350 and 400 nm (Figure 1). The
carrier of this transient absorption has a lifetime in excess of
many microseconds at 295 K. The lifetime (τ) of this intermedi-
ate can be reduced significantly in the presence of diethylamine
(DEA) and a plot of 1/τ versus [DEA] is linear. This behavior
calculated to be 2.8 kcal/mol lower in energy than 14c.
Presumably, at least part of this energy difference is due to
greater destabilizing interactions between the cyano and imino
groups when they are ortho, rather than para, to each other.
However, concentration of spin density at the central carbon of
a cyclohexadienyl radical probably also makes the para cyano
group in 14e more radical stabilizing than the ortho cyano group
1
in 4c.
The CASPT2 energy difference of 3.4 kcal/mol between 14d
1
1
1
and 4e is even larger than that between 4c and 4e. Steric
effects are unlikely to play any role in the energy difference
between 14d and 14e, and this energy difference is almost
certainly a consequence of the much greater stabilization of the

Cyano-Substituted Singlet Phenyl Nitrenes
J. Am. Chem. Soc., Vol. 123, No. 7, 2001 1429
very similar to the spectrum of triplet o-cyanophenylnitrene 34c,
(although 14c may also have some absorption between 300 and
350 nm). The same intermediate is formed as a persistent species
upon brief (10 s) photolysis (254 nm) of o-cyanophenyl azide
in glassy methylcyclohexane at 77 K (Figure 2, spectrum 3).
This intermediate is confidently assigned as 34c by comparison
of its spectrum to that of unsubstituted triplet phenylnitrene (308
nm)3e,k
LFP of 2,6-dicyanophenyl azide gave results similar to those
found in the LFP study of o-cyanophenyl azide. LFP of the
dicyano azide at 295 K produces a broad transient absorption
with maximum at 360 nm (similar to those of Figure 1) which
could be assigned to didehydroazepine 7f. Azepine 7f reacts
with DEA even more rapidly than a monocyanodidehy-
droazepine and, as expected,3g with a rate constant close to the
diffusion limit (Table 2).
The transient spectra obtained at 185 K are shown in Figure
3. The short-lived, structured band with maxima at 362, 384,
and 405 nm (Figure 3, spectrum 1) is assigned to singlet 2,6-
dicyanophenylnitrene (14f). The long-lived band at 340 nm
(Figure 3, Spectrum 2), which is persistent in a glass at 77 K
Figure 1. OMA spectrum detected after LFP of 2-cyanophenyl azide
in pentane at 295 K, 50 ns after the KrF laser pulse (249 nm) with a
200 ns time window. The solid line is drawn through the averaged
experimental points.
3
(Figure 3, Spectrum 3), is attributed to 4f. The absorption
is characteristic of didehydroazepines such as 3.2g-i The
didehydroazepine transient is formed at 295 K faster than the
time resolution of the spectrometer (1-2 ns). The rate constant
of its reaction with DEA is very high and equal to (3.5 ( 0.3)
× 109 M-1 s-1 (Table 2). This value is what one would expect
for reaction of cyano-substituted didehydroazepine with DEA
on the basis of the work of Li, Poliakoff, and Schuster with
related didehydroazepines.3g
The UV-vis spectra of didehydroazepines 7c and 8c (derived
from 5c and 6c, respectively, Scheme 2), are expected to be
very similar; thus, we cannot confidently assign the spectrum
to one or the other. Chemical trapping studies, discussed in the
next section, indicate that the transient spectrum probably
contains contributions from both species (vide infra). Kinetic
curves for 3H-azepine formation in the presence of DEA
appeared to be single exponentials. This finding indicates that
the rate constants of the reaction of isomeric didehydroazepines
with DEA are very similar.
LFP of o-cyanophenyl azide in pentane at 185 K produces a
transient spectrum which contains a sharp, structured band, with
maximum absorbance at 325 nm, and a broader band, with an
absorbance between 350 and 400 nm (Figure 2, spectrum 1).
The band observed between 350 and 400 nm at 185 K is more
structured and decays much more rapidly than the band observed
in the same wavelength region at 295 K. Thus, the transient
that absorbs between 350 and 400 nm at 185 K cannot be a
didehydroazepine, and this absorbance is assigned instead to
singlet o-cyanophenylnitrene (14c). This absorption cannot be
assigned to either benzazirines 5c or 6c because matrix-isolated
difluorobenzazirine has λmax ) 280 nm.22 Our CIS/6-311+G*
calculations23 of the spectra of substituted benzazirines dem-
onstrate no significant influence of fluoro- and cyano substit-
uents on the spectra. According to these calculations parent
benzazirine has maximum at 269 nm, fluoro-substituted ben-
zazirine, at 273 nm, and 6c, at 259 nm.
spectra of the cyano-substituted singlet phenylnitrenes are very
similar to that of unsubstituted singlet phenylnitrene which has
λmax ) 337, 352 nm.
It is interesting to note that cyano substitution leads to a red
shift of the UV spectra of both the singlet and triplet phenyl
nitrenes. This is readily understood by noting that both singlet
and triplet substituted phenylnitrenes have similar open-shell
electronic configurations. According to CASSCF/CASPT2
calculations,3k all of the calculated bands of singlet phenylnitrene
have the same assignment as the corresponding bands of triplet
phenylnitrene, but their positions are shifted to the red by about
0.8 eV.
At subambient temperatures, formation of didehydroazepines
3
(7c, 8c, 7f) and triplet nitrenes (34c and 4f) was no longer
instantaneous (Figure 4). The decays of the singlet nitrenes 14c
1
and 4f were monitored at 380 and 405 nm, (Figure 4, curve
1), respectively. The formation of the reaction products (Figure
4, curve 2) were exponential and were analyzed to yield
observed rate constants kOBS of singlet nitrene disappearance.
The temperature dependence of kOBS for the decay of 4c and 4f
is shown in Figure 5.
In the LFP of p-cyanophenyl azide at ambient and subambient
temperature, it was not possible to detect the decay of the
transient absorption of 14e. However, it was possible to resolve
the growth of didehydroazepine 7e and 34e absorption, even at
ambient temperature (Figure 6). The absorption growth was fit
to an exponential function and analyzed to give an observed
rate constant of kOBS ) (1.3 ( 0.6) × 108 s-1 at ambient
temperature, which corresponds to a lifetime of 8 ( 4 ns for
1
singlet nitrene 4e. The spectrum of Figure 6 is similar to the
spectra of other didehydroazepines and was assigned to 7e. The
rate constant of reaction of 7e with DEA is (1.6 ( 0.2) × 109
M-1 s-1, and it fits well to the same correlation with the
Hammett σ value as the rate constants for other 5-substituted
1,2-didehydroazepines.3g
Singlet o-cyanophenylnitrene has an absorption maximum
(∼370 nm) at longer wavelength than unsubstituted singlet
phenylnitrene (337, 352 nm).3k Decay of the transient assigned
Because we measured the absorption growth of the products
for reaction of 14e, rather than decay of the transient absorption
due to 14e, the data for the p-cyanonitrene are less precise than
those for the o-cyano- (14c) and the 2,6-dicyanophenylnitrene
(14f) systems. It is very clear, however, that singlet p-
cyanophenylnitrene has the longest lifetime of all of the singlet
phenylnitrenes studied in this work. The temperature dependence
1
to 4c results in a spectrum (Figure 2, spectrum 2) which is
(22) Morawietz, J.; Sander, W. J. Org. Chem. 1996, 61, 4351.
(23) Foresman, J. B.; Head-Gordon, M.; Pople, J. A.; Frish, M. J. J.
Phys. Chem. 1992, 96, 135.

1430 J. Am. Chem. Soc., Vol. 123, No. 7, 2001
Gritsan et al.
Table 2. Summary of Kinetic Results for Singlet Cyano-Substituted Phenylnitrenes and Didehydroazepines
nitrene
λ
max, nm
τ(295), ns
kISC × 10-6, s-1
log A, s-1
Ea, cal/mol
kDEA × 10-9, M-1 s-1
solvent
o-cyano (14c)
380
-
405
405
405
∼ 2a
8 ( 4
∼ 2.5a
∼ 2.3a
∼ 2.3a
2.8 ( 0.3
6 ( 2
12.8 ( 0.3
13.5 ( 0.6
13.3 ( 0.2
13.5 ( 0.2
13.1 ( 1.0
5500 ( 300
7200 ( 800
6400 ( 300
6500 ( 400
6000 ( 1100
3.5 ( 0.3
1.6 ( 0.2
C5H12
C5H12
CH2Cl2
C5H12
THF
p-cyano (14e)
2,6-dicyano (14f)
2,6-dicyano (14f)
2,6-dicyano (14f)
4.5 ( 0.5
6.2 ( 0.8
5.9 ( 1.5
8.3 ( 0.8
a Lifetime estimated by extrapolation of the data to 295 K.
Figure 2. OMA spectra detected after LFP of 2-cyanophenyl azide in
pentane at 185 K (1) just after the laser pulse (249 nm) with a 100 ns
time window and (2) 300 ns after the laser pulse with 100 ns window.
(3) The differential absorption spectrum of triplet nitrene detected after
brief (10 s) stationary photolysis (254 nm) of 2-cyanophenyl azide in
methylcyclohexane at 77 K.
Figure 4. Changes in transient absorption at 405 nm (1) and 340 nm
(2) after LFP of 2,6-di-cyanophenyl azide (1c) in CH2Cl2 at 213 K.
Figure 5. Plots of kOBS versus 1/T for (1) para-cyanophenylnitrene
and (2) o-cyanophenylnitrene in pentane and for (3) 2,6-dicyanophe-
nylnitrene in CH2Cl2.
of the singlet to the triplet. For each nitrene kOBS is equal to the
sum of elementary rate constants kC and kISC (kOBS) kC + kISC).
The bicyclic azirine intermediates pictured in Scheme 2 were
1
1
not detected in the LFP of 4c and 4f. The observed rate
constant for cyclization of each of these singlet nitrenes is the
same as the observed rate constant for the appearance of the
didehydroazepine. As with parent singlet phenylnitrene kC ,
kE. We could not detect the decay of the singlet p-cyanophe-
Figure 3. OMA spectra detected after LFP (249 nm) of 2,6-
dicyanophenyl azide in CH2Cl2 at 185 K (1) just after the laser pulse
with 100 ns time window and (2) 500 ns after the laser pulse with 100
ns window. (3) The differential absorption spectrum of triplet nitrene
detected after brief (20 s) stationary photolysis (254 nm) of 2,6-
dicyanophenyl azide in methylcyclohexane at 77 K.
1
nylnitrene 4e, but we assume that kC , kE in this case, too.
The temperature dependence of kOBS for p-cyanophenylnitrene
14e is also depicted in Figure 5. The temperature-independent
region of Figure 5 is associated with kISC, and all the temperature
dependence is attributed to kC. Plots of ln(kOBS - kISC) versus
1/T for 4c, 4e, and 4f are linear (Figure 7), which indicates
that kISC is constant over the entire temperature range. From
these plots Arrhenius parameters for cyclization of 14c, 14e, and
14f can be extracted. These activation parameters are given in
Table 2.
of kOBS for p-cyanophenylnitrene 4e is also depicted in Figure
5. At all temperatures, singlet nitrene lifetimes increase in the
order o-cyanophenyl < 2,6-dicyanophenyl < p-cyanophenylni-
trene.
Scheme 2 shows the two decay pathways for singlet cy-
anophenylnitrenes. As defined in Scheme 2, kC is the rate
constant for cyclization to form the bicyclic azirine intermediates
(5 and 6), and kISC is the rate constant for intersystem crossing
1
1
1

Cyano-Substituted Singlet Phenyl Nitrenes
J. Am. Chem. Soc., Vol. 123, No. 7, 2001 1431
Figure 6. Transient spectrum produced by LFP (249 nm) of para-
cyanophenyl azide in pentane at 246 K taken over a 100 ns window
immediately after the laser pulse. Insert: Change in transient absorption
at 355 nm following LFP (249 nm) of para-cyanophenyl azide in
pentane at 223 K.
Figure 8. Plots of kOBS versus 1/T for 2,6-dicyanophenylnitrene in
different solvents: pentane (open circles), CH2Cl2 (solid circles), and
THF (triangles).
Table 3. Product Ratios of 3H-Azepinesa Formed upon Photolysis
of o-Cyanophenyl Azides at Ambient Temperature in the Presence
of 0.1 M Diethylamine
a A species with the same fragmentation pattern as 10c was also
detected by GC-MS, but attempts to isolate this compound failed. It
is attributed to the 1H-azepine analogue of 10c which is formed initially
and isomerizes to 10c. The data in the table is the sum of the 1H and
3H-azepine yields. 1H-Azepines related to 9c were not observed by
GC-MS.
Figure 7. Arrhenius treatment of kR () kOBS - kISC) data for (1) para-
cyanophenylnitrene and (2) o-cyanophenylnitrene (2) in pentane and
for (3) 2,6-dicyanophenylnitrene in CH2Cl2.
the same in pentane and methylene chloride. The activation
barrier to cyclization of 2,6-dicyanophenylnitrene is 6.0 ( 1.1
kcal/mol in THF, and is 6.5 ( 0.4 kcal/mol in pentane and
methylene chloride (Table 2). The barrier to cyclization of parent
singlet phenylnitrene is 5.6 ( 0.3 kcal/mol in pentane. Fluo-
rescence increases the error in the data obtained in THF for
2,6-dicyanophenylnitrene.
The activation parameters for cyclization of o-cyano- (14c)
and 2,6-dicyanophenylnitrene (14f) are similar. The fact that both
the log(A) and Ea for 4c are less than those for 4f suggests
1
1
that the data may be influenced by systematic error. If log(A)
1
1
for 4f is set equal to 12.8, the same value as for 4c, the
calculated Ea value for 14f is reduced from 6.4 to 5.9 kcal/mol.
Although this activation energy for cyclization of 14f is still
Chemical Trapping Studies
1
larger than that for cyclization of 4c by 0.4 kcal/mol, within
experimental error the barriers to cyclization of these two singlet
nitrenes are the same as each other and as the barrier of 5.6 (
0.2 kcal/mol for cyclization of unsubstituted singlet phenylni-
trene (11).3i,k These results confirm that, as predicted compu-
tationally, the effects of cyano and fluoro substituents on
phenylnitrene cyclizations are very different. Whereas the pair
of ortho fluoro substituents in singlet 2,6-difluorophenylnitrene
retard the rate of cyclization, the pair of ortho cyano substituents
As mentioned earlier, Smalley and co-workers14a have already
confirmed the computational prediction, that cyclization of 14c
toward the ortho cyano group should be competitive with
cyclization away from it. Smalley and co-workers analyzed the
products formed upon photolysis of o-cyanophenyl azide in
mixtures of water and tetrahydrofuran. They found that the
products were generated by trapping of didehydroazepine
1
intermediates 7c and 8c, formed by cyclization of 4c both
toward and away from the cyano group.
1
in 4f have little or no effect on the barrier to cyclization.
However, the barrier to cyclization of singlet p-cyanophe-
In our hands photolysis of o-cyanophenyl azide in the pre-
sence of diethylamine gives 3H-azepine trapping products, 9c
and 10c (Scheme 2). Variation of the solvent leads to subtle
variation in the product distribution. The solvent effect on the
relative rates of cyclization toward and away from the cyano
group is small, but finite. The compositions of the mixtures
formed under different reaction conditions are shown in Table
3.
nylnitrene (14e) is 1-2 kcal/mol greater than those measured
1
1
1
for 1, 4c, and 4f. There is no doubt that, as predicted both
qualitatively and by the CASPT2 calculations, a para cyano
group does indeed retard the rate of singlet phenylnitrene
cyclization.
Variation of solvent has only a small effect on the kinetics.
Values of kOBS obtained upon LFP of 2,6-dicyanophenyl azide
in pentane, methylene chloride, and tetrahydrofuran are shown
in Figure 8. Values of kOBS are largest in THF and are about
Younger and Bell have presented chemical evidence that the
cyclization of 3-acetamido-4-trifluoroacetamido phenylnitrene

1432 J. Am. Chem. Soc., Vol. 123, No. 7, 2001
Gritsan et al.
didehydroazepines 7c and 8c upon photolysis of o-cyanophenyl
azide in the presence of diethylamine. One other product, 12c,
was isolated upon photolysis of o-cyanophenyl azide in the
presence of diethylamine.
This type of minor product has been observed previously in
the reactions of electron-deficient arylnitrenes with diethylamine.
It has been attributed to electron-transfer reactions of the triplet
nitrene.7a,b,27
Conclusions
The results of our LFP experiments confirm the predictions,
based on both qualitative theory and our quantitative CASPT2
calculations, regarding the effects of cyano substituents on the
rate of phenylnitrene cyclization. We find that cyclization at a
substituted ortho carbon is much faster when the substituent is
cyano, rather than methyl8b or fluoro.10b Our kinetic result, that
cyclization at an ortho carbon occurs about as fast in singlet
2,6-dicyanophenylnitrene (14f) as in singlet phenylnitrene
(11),3i-k is consistent with the results of our chemical trapping
experiments. Like Smalley and co-workers,14a we find that in
singlet o-cyanophenylnitrene (14c) cyclization at the substituted
and unsubstituted ortho carbons are competitive.
Figure 9. A plot of 11c/(9c + 10c) versus the concentration of
diethylamine.
to two isomeric azirines is reversible.4d Our laboratory has
presented kinetic evidence that cyclization of o-fluorophenylni-
trene (14b f 5b) is also reversible.10b However, there is no
evidence from our LFP studies for reversibility in the cyclization
of o-cyanophenylnitrene (14c). In addition, the ratio of azepines
9c and 10c, formed in pentane, does not change over a
diethylamine (DEA) concentration range of 0.05-0.40 M. Thus,
our chemical trapping studies also indicate that cyclization of
14c is irreversible under the reaction conditions used in the
chemical trapping experiments.
In contrast to the effect of ortho cyano substitution, cyano
substitution at the para carbon of phenylnitrene (11) makes the
rate of cyclization of singlet p-cyanophenylnitrene (14e) measur-
At high DEA concentrations hydrazine product 11c is formed.
Phenylnitrene is known to insert into the N-H bond of
diethylamine in low yield.24 Moderate yields of hydrazines are
also realized with perfluorophenylnitrene,7a,26 p-nitro- and
p-cyanophenylnitrene.25 In the latter case, there has been
speculation that the interconversion of the singlet nitrene (14c)
and benzazirine 5c might be reversible.2a,25,26 A plot of 11c/(9c
+ 10c) versus the concentration of diethylamine is linear (Figure
9) with a slope of 0.038 ) kH/kC, where kC is the sum of the
rate constants for cyclization of 14c to 5c and 6c, and kH is the
1
ably slower than that of 1. The origin of the opposite effects
of ortho and para cyano groups is the same. A cyano substituent
is radical-stabilizing and thus tends to localize an unpaired π
electron at the carbon to which the cyano group is attached. In
the case of an ortho cyano group, this facilitates cyclization at
the substituted carbon. However, a para cyano group diminishes
the unpaired π spin density at both ortho carbons and thus
retards the rate of nitrene cyclization.
1
rate constant for reaction of 4c with DEA to form hydrazine
Experimental Section
11c. If we assume that kH ) 107 - 108 M-1 s-1, as it is in the
reaction of fluorinated aryl nitrenes with pyridine,7c-e we deduce
that kC ) 2.6 × (108-109) s-1. Thus, the deduced lifetime of
singlet o-cyanophenylnitrene (14c) is between 0.4 and 4 ns at
ambient temperature, a value that is in reasonable agreement
with the lifetime derived from the LFP experiments.
Laser Flash Photolysis. A Nd:YAG laser (Continuum PY62C-10,
35 ps, 10 mJ, 266 nm), KrF (Lumonix, 12 ns, 50 mJ, 249 nm) and
XeCl eximer lasers (Lambda Physik, 20 ns, 50 mJ, 308 nm) were used
as the excitation light sources. The laser apparatus system at The Ohio
State University has been previously described in detail.7c
Typically, the solution was contained in a quartz cuvette which was
placed in a quartz cryostat. Temperature was varied in the range of
150-300 K and kept to within (1 Κ by passing a thermostabilized
nitrogen stream over the cuvette. The sample solutions were changed
after every laser shot, to avoid effects due to the accumulation of
photoproducts. The absorption spectra of long-lived (τ > 300 ns)
intermediates were measured using an eximer KrF or XeCl lasers in
conjunction with an optical multichannel analyzer (EG & G Princeton
Applied Research model 1460).
Low-Temperature Photolysis. Low-temperature (77 K) photolysis
was performed in a liquid nitrogen-filled cryostat with plane-parallel
quartz windows. Thin-walled 2 mm quartz sample cuvettes were
employed. Methylcyclohexane was used as a solvent. Rayonet 254 nm
lamps were used to photolyze the samples, and UV-vis spectra were
recorded with a Lambda 6 UV-vis spectrophotometer.
Also formed, but only in trace amounts, were o-diaminoben-
zene products, derived from trapping 5c and 6c, rather than
(24) (a) Odum, R. A.; Brenner, M. J. Am. Chem. Soc. 1966, 88, 2074.
(b) Sundberg, R. J.; Smith, R. H., Jr. J. Org. Chem. 1971, 36, 295.
(25) (a) Odum, R. A.; Wolf, G. J. Chem. Soc., Chem. Commun. 1973,
360. (b) Odum, R. A.; Aaronson, A. M. J. Am. Chem. Soc. 1969, 91, 5680.
(c)Liang, T.-Y.; Schuster, G. B. J. Am. Chem. Soc. 1986, 108, 546; 1987,
109, 7803.
Materials. Alkane solvents were used as received, but methylene
chloride was purified by passage through a column of alumina.
2-Cyanophenyl azide14 and 4-cyanophenyl azide25 were prepared by
(26) Abramovitch, R. A.; Challand, S. R.; Scriven, E. F. V. J. Am. Chem.
Soc. 1972, 94, 1374.

Cyano-Substituted Singlet Phenyl Nitrenes
J. Am. Chem. Soc., Vol. 123, No. 7, 2001 1433
known procedures from the corresponding commercially available
purified by preparative TLC (SiO2, 20 × 20 cm, 80% cyclohexane-
20% ethyl acetate). The yield of 10c was 0.04 g (10%), as a colorless
oil: 1H NMR (500 MHz, CDCl3) δ 1.01 (br, 3H), 1.15 (br, 3H), 2.65
(br, 2H), 3.27 (br, 2H), 3.36 (br, 2H), 5.32 (dd, J ) 15.6, J ) 7.6,
1H), 6.28 (m, 2H);13C NMR (125 MHz, CDCl3) δ 12.86, 14.51, 32.00,
43.80, 44.47, 118.15, 119.61, 120.66, 126.20, 128.39, 147.28; EIMS
m/z (rel intens) 189 (M+, 46), 174 (9), 160 (33), 146 (12), 132 (24),
118 (100), 105 (36), 90 (15), 72 (38); HRMS calcd for C11H15N3
189.1267, found 189.1270.
1
anilines. The azides were characterized with IR, H NMR, 13C NMR
spectroscopy, and the spectra were compared with those reported
previously in the literature. 2,6-Dicyanoaniline was prepared by the
method of Griffiths et al.28
2,6-Dicyanophenyl Azide. To a stirred suspension of 2,6-dicyano-
aniline28 (0.3 g) in HCl (37%, 3.06 mL) was added dropwise at 0 °C,
a solution of sodium nitrite (126.5 mg in 2.25 mL of water). The
solution was stirred a further 10 min and then filtered. To the stirred
filtrate was added a solution of sodium azide (450 mg in 3.36 mL of
water). The mixture was stirred for 2 more hours and filtered. The water-
insoluble filter cake was dissolved in chloroform and filtered, and the
filtrate was rotary-evaporated. The solid obtained was recrystallized
from benzene:petroleum ether (1:1), and 84.8 mg of crystals were
obtained. (27% yield, melting point: 113 °C). The IR spectrum gave
Photolysis of 2-Cyanophenyl Azide in Neat Diethylamine. A
solution of 2-cyanophenyl azide (0.144 g, 1 mmol) in diethylamine
(20 mL), freshly distilled from LiAlH4, was purged with argon and
photolyzed in a Pyrex vial at 350 nm for 22 h at 10-12 °C using a
Rayonet reactor. The solvent was removed on the rotary evaporator,
and the mixture was separated by preparative TLC (SiO2, 20 × 20 cm,
90% cyclohexane-10% ethyl acetate). The first major TLC band
yielded (2-cyanophenyl) 2,2-diethylhydrazine (11c) (16 mg, 8.5%) as
a white solid: mp 33-35 °C;1H NMR (500 MHz, CDCl3) δ 1.03 (t, J
) 7.1, 6H), 2,71 (br, 4H), 5.00 (s, exchanged with D2O, 1H), 6.63 (m,
1H), 7.22 (m, 1H), 7.32 (m, 2H);13C NMR (125 MHz, CDCl3) δ 12.10,
52.80, 92.53, 113.30, 117.27, 117.63, 132.10, 134.01, 152.21; EIMS
m/z (rel intens) 189 (M+, 100), 174 (71), 160 (39), 146 (27), 131 (12),
117 (85), 102 (12), 90 (34); HRMS calcd for C11H15N3 189.1267, found.
189.1268. The second major TLC band yielded N,N-diethyl-N′-(2-
cyanophenyl) acetamidine (21.5 mg, 10%) as colorless oil: 1H NMR
(200 MHz, CDCl3) δ 1.23 (t, J ) 7.1, 6H), 1.91 (s, 3H), 3.44 (q, J )
7.1, 4H), 6.78 (m, 1H), 6.93 (m, 1H), 7.39 (m, 1H), 7.45 (m, 1H);13C
NMR (125 MHz, CDCl3) δ 13.76, 15.51, 43.08, 106.33, 119.14, 121.45,
123.81, 133.09, 133.56, 156.40; EIMS m/z (rel intens) 215 (M+, 30)
186 (16), 143 (100), 102 (35), 86 (8) 85 (8), 72 (20) HRMS calcd for
C13H17N3 215.1418, found 215.1424. The third major TLC band gave
2-aminobenzonitrile (27 mg, 23%).
an azide absorption at 2149 cm-1 and cyano absorption at 2237 cm-1
.
The 1H NMR spectrum (CDCl3) showed peaks at δ 7.83 (2H, d), 7.35
(1H, t) but no peak at δ 6.80, belonging to amine hydrogens of starting
material. 13C NMR gave peaks at δ 143.8, 138.3, 125.5, 113.8, 107.0.
HRMS calcd for C8H3N5 169.0388, found 169.0392.
Isolation of 3-Cyano-2-diethylamino-3H-azepine (9c). An argon-
purged solution of 2-cyanophenyl azide (0.144 g, 1 mmol) and
diethylamine (0.41 mL, 4 mmol) in dry pentane (40 mL, Aldrich) was
irradiated with Pyrex-filtered 350 nm light in the Rayonet reactor at
10-12 °C. After 17 h the reaction flask surface almost lost transparency
due to the build-up of the dark brown film. The solution was placed in
another dry flask, purged with argon, and irradiated for an additional
16 h. The flask was replaced one more time, followed by irradiation
of the sample for another 17 h. The mixture was concentrated on the
rotary evaporator and separated by preparative TLC (SiO2, 20 × 20
cm, 63% benzene-33% cyclohexane-4% triethylamine). The yield
of 9c was 31 mg (16%), as a colorless oil: 1H NMR (500 MHz, CDCl3)
δ 1.15 (t, J ) 7.1, 6H), 3.37 (m, 4H), 5.05 (t, J ) 8.5, 1H), 5.16 (br,
1H), 5.92 (dd, J ) 7.5, J ) 6.4, 1H), 6.51 (dd, J ) 8.4, J ) 6.4, 1H),
7.29 (d, J ) 8.1, 1H); 13C NMR (125 MHz, CDCl3) δ 13.34, 31.82,
44.07, 106.03, 109.68, 113.69, 131.37, 137.18, 141.25; EIMS m/z (rel
intens) 189 (M+, 68), 174 (25), 160 (71), 149 (90), 146 (24), 135 (31),
132 (100), 118 (69), 105 (75), 90 (29); HRMS calcd for C11H15N3
189.1267, found 189.1262.
Isolation of 7-Cyano-2-diethylamino-3H-azepine (10c). A solution
of 2-cyanophenyl azide (0.3 g, 2.08 mmol) and diethylamine (0.22 mL,
2.12 mmol) in dry THF (20 mL), freshly distilled from benzophenone
ketyl, was degassed by the freeze-thaw method in a flame-dried Pyrex
tube, which was then filled with argon. The mixture was photolyzed
with 350 nm light in the Rayonet reactor for 20 h at 10-12 °C. After
the solvent was removed under reduced pressure, the residue was
chromatographed on a 1 in. × 8 in. column of silica gel (eluent: 80%
pentane-20% ether). Fractions enriched with 7-cyano-2-diethylamino-
3H-azepine (determined by GC) were combined, concentrated, and
Acknowledgment. Support of this work in Columbus and
Seattle by the National Science Foundation is gratefully
acknowledged. W.L.K. is grateful to the University of San
Francisco Faculty Development Fund and The Lily Drake
Cancer Research Fund for generous financial support. N.P.G.
gratefully acknowledges the support of the National Research
Council, and Russian Foundation for Basic Research.
Supporting Information Available: CASSCF-optimized
Cartesian coordinates for singlet nitrenes, bicyclic azirines, and
transition states discussed in the text, and a table of CASSCF
and CASPT2 absolute energies, a table with the wavelengths
and oscillator strengths calculated by CIS method for substituted
benzazirines, and the plot of observed rate constants versus DEA
concentrations for the reaction of cyano-substituted didehy-
droazepines are available (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
(27) Polanc, S.; Stanounik, B.; Tisler, M. J. Org. Chem. 1976, 41, 3152.
(28) Griffiths, J.; Lockwood, M.; Roozpeiker, B. J. Chem. Soc., Perkin
Trans 2 1977, 1608.
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